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| Mosaic skin disorders - deep sequencing v2.2 | ARAF | Arina Puzriakova Tag treatable tag was added to gene: ARAF. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mosaic skin disorders - deep sequencing v2.2 | ARAF | Arina Puzriakova Classified gene: ARAF as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mosaic skin disorders - deep sequencing v2.2 | ARAF |
Arina Puzriakova Added comment: Comment on list classification: New gene added by Tom Cullup (GOSH). ARAF is not currently associated with any phenotype in OMIM or G2P. Although only two patients have been reported with the same missense variant, functional studies including an animal model provide strong support of pathogenicity (outlined below). Evidence of this variant specific gene-disease relationship is sufficiently compelling but the phenotype is more within scope of the R110 Segmental overgrowth disorders – Deep sequencing panel. Therefore rating as amber on this panel and green on R110. - PMID: 31263281 (2019): To date, only two unrelated patients have been reported with the same missense GoF variant in ARAF (c.640T>C:p.S214P) who both had a complex lymphatic anomaly (no haplotype analysis was done). Cells transduced with ARAF-S214P showed elevated ERK1/2 activity, enhanced lymphangiogenic capacity, and disassembly of actin skeleton and VE-cadherin junctions. A zebrafish model recapitulated the lymphatic phenotype. The cellular, zebrafish and patient clinical phenotypes were all rescued with with a MEK inhibitor. |
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| Mosaic skin disorders - deep sequencing v2.2 | ARAF | Arina Puzriakova Gene: araf has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mosaic skin disorders - deep sequencing v2.1 | ARAF |
Tom Cullup gene: ARAF was added gene: ARAF was added to Mosaic skin disorders - deep sequencing. Sources: Expert list Mode of inheritance for gene: ARAF was set to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males) Publications for gene: ARAF were set to 31263281 Phenotypes for gene: ARAF were set to central conducting lymphatic anomaly Penetrance for gene: ARAF were set to unknown Mode of pathogenicity for gene: ARAF was set to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments Review for gene: ARAF was set to GREEN Added comment: Two patients described in Li et al with lymphatic anomaly, with same activating missense; functional studies support activating effect including zebrafish model. Sources: Expert list |
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